DESCRIPTION: (Applicant's Abstract) The limbic system is of central importance in the experience of sensation, affect, and memory. Previous investigators have suggested that a state of permanent limbic neuronal hyperexcitability may be present in cocaine addicts, such that spontaneous or cue-related episodes of limbic neuronal discharge may occur. Limbic discharge may subsequently induce craving in cocaine dependent patients, precipitating relapse to drug use. Hypothesis: We hypothesize that (1) patients with a history of cocaine abuse or dependence will demonstrate greater procaine-induced limbic activation compared to healthy controls, and (2) there will be a positive correlation between procaine-induced limbic activation and the amount of previous lifetime cocaine use. Preliminary Data: Our preliminary data (NIDA R21) (n=29) suggests (1) procaine produces increased limbic rCBF in female controls compared to male controls, (2) patients with a non-aversive response to procaine demonstrate increased limbic, particularly left amygdalar, rCBF compared to patients with an aversive response to procaine, and (3) baseline orbital frontal and temporal rCBF is decreased in patients at baseline, and these differences lessen following procaine This grant proposes to extend our sample size in men and women to conclusively confirm our hypotheses in both genders. Procedure: Female and male patients, ages 25-45 y/o, will be compared to age and sex matched healthy controls. The limbic system will be activated by the local anesthetic procaine, a relatively specific stimulant of the limbic system. Regional cerebral blood flow (rCBF) following both procaine and saline will be assessed using Single Photon Emission Computerized Tomography (SPECT) neuroimaging techniques Differences in brain images will be analyzed using both traditional Region of Interest (R0I) and two newer statistical approaches: ratio of rCBF to global CBF and Statistical Parametric Mapping (SPM). Subjects will also be assessed for physiologic changes, changes in mood and sensorium, and the similarity of the experience to other drug experiences. ROIs will be identified by co-registration with MRIs. Significance: An association between limbic system sensitivity and previous cocaine use would provide the framework for subsequent studies to examine the relationship between procaine-induced limbic response and relapse, as well as suggesting novel pharmacologic approaches to treat cocaine addiction.